Through global transcriptome analysis, we have identified two gene signatures that can predict BET bromodomain inhibitor-sensitive and -resistant small cell lung cancer cell lines with 100% and 88% accuracy, respectively. We have also been studying the underlying mechanism(s) by which these biomarkers determine sensitivity to BET bromodomain inhibitor. In addition, we did a high-throughput matrix combination screening in collaboration with NCATS. Several FDA approved drugs were found to synergize with BET bromodomain inhibitor. We are in the process of studying the underlying mechanism and exploring its clinical application.